Animal feeds and methods



United States Patent 3,248,223 ANIMAL FEEDS AND METHODS Jacob Christopher Bauernfeind, GlenRock, N.J., assignor to Holfmann-La Roche Inc., Nutley, N..l., a corporation of New Jersey No Drawing. Filed Apr. 11, 1962, Ser. No. 186,652 8 Claims. (Cl. 99-2) This invention relates to animal feeds and to methods of feeding animals. More particularly, the invention relates to growth-promoting agents and animal feed compositions containing a growth-promoting agent; to feed supplements containing a growth-promoting agent which can be administered with conventional animal feeds or conventional rations for animals or nutrients or other diluentmaterials suitable for oral ingestion by animals, such feed supplements thus being useful also to prepare the animal feed compositions of the invention; and to improved methods of growing animals by feeding them the animal feed compositions or feed supplement of the invention.

The growth-promoting agents employed above or in the feed compositions and supplements of the invention have the following formula wherein X is nitro or halogen; R is hydrogen or lower alkyl, preferably methyl; and Y is hydrogen, trifluoromethyl, or halogen. The term halogen used above for X and/or Y includes fluorine, chlorine, bromine, or iodine, with chlorine preferred.

Examples of compounds having the above structure include 7-chloro-5-phenyl-l-methyl-3I-I-1,4-benzodiazepin- 2(lH)-one; 7-nitro-5-(u,a,a trifluoro-o-tolyl) 3H 1,4- benzodiazepin-2(lH)-one; 7-nitro-5 (2 chlorophenyl)- 3H-1,4-benzodiazepin-2(1H)-one, etc.

The animals for which the present compositions and methods are intended are economically useful animals and birds, e.g., ruminants such as cattle and sheep, and monogastric animals and birds such as pigs and turkeys. The term animal as used hereinafter is understood to include economically useful animals and birds.

The animal feed compositions of the invention can be made by mixing a compound of Formula I with conventional ingredients of animal feeds. The mixing can be accomplished by methods known per se. Conventional methods of making the improved animal feeds of themvention comprise charging conventional feed ingredients and a compound of Formula I into a batch mixer and operating the mixer until the contents thereof are uniformly dispersed to give a mixture which is homogeneous throughout. An alternative mixture of preparing animal feeds according to the invention comprises adding a feed supplement containing a compound of Formula I to a conventional animal feed or administering the supplement to the animal directly. Thus, it will often be convenient to premix the compounds of Formula I with a present invention.

3,248,223 Patented Apr. 26, 1966 diluent which is suitable for oral ingestion by the animal (this diluent may itself be a nutrient material for the animal) and subsequently to mix the premixed supplement so-obtained with a commercially obtainable conventional animal feed material so as to obtain the improved animal feed compositions of the invention. As another alternative, a compound of Formula I may be intimately admixed with a material such as corn meal or soy bean oil to give a uniformly blended composition, and the feed supplement composition containing a compound of Formula I so-obtained may be subsequently mixed with additional nutrient ingredients suitable to make a finished improved feed according to the invention. Preferably the compound of Formula I is employed in the feed supplement or finished feed in an amount that will supply the animal with a daily intake of about 1 mg. to about mg., preferably about 2 mg. to about 50 mg, per head per day. This can generally be accomplished by providing from about 1 mg. to about 100 mg. of a compound of Formula I per pound of finished feedrbut it should be understood that the invention embraces the use of any proportion of compound of Formula I that will give beneficial and economically desirable results in the utilization by the animal of its feed. An especially preferred proportion of compound of Formula I in the feed is from about 2 mg. to about 50 mg. per pound of finished feed.

The novel methods of the invention whereby a compound of Formula I is made a part of the animals diet can be practiced by feeding growing animals on complete animal feed rations, improved by incorporation of the compound of Formula I therein according to the Alternatively, it may be desirable in some cases to feed the animal a feed composition con taining a compound of Formula I, which contains less nutrient material than is found in the animals total diet. For example, the animal can be fed alternately on conventional rations and on compositions of the invention containing a compound of Formula I, or the compound of Formula I can be dispensed in the animals drinking water and can be furnished to the animal in this way.

Diethyl stilbestrol is a commonly used growth-promoting agent in animal feeds. It has also been found that the addition of from about 1 mg. to about 100 mg. per head per day of a compound of Formula I in addition to the usual level of 10 mg. of diethyl stilbestrol per head per day to conventional animal feeds produces a marked increase in animal growth over that obtained with diethyl stilbestrol alone. However, as discussed above, a compound of Formula I can be employed alone in the compositions of the invention Without the presence of any diethyl stilbestrol.

The growth-promoting agents of the invention can also be used in conjunction with other feed additives, e.g., anti biotics, hormones, enzymes, arsenicals, coccidiostats, etc.

Preferred aspects of the invention relate to cattle feed compositions comprising cattle nutrients and a compound of Formula I and to methods of growing cattle by feeding them such compositions. It has been found that cattle growing on animal feed compositions comprising conventional rations and, in addition, a compound of Formula I consume feed with greater efficiency, i.e., it takes less feed when employing the cattle feed of the compositions to procure a desired gain in weight of the cattle than when employing conventional cattle feed compositions.

The following examples are illustrative but not limitative of the invention.

In the following examples the animals given in the EXAMPLE 4 examples were fed with the feed rations shown therein 700 lb beef cattle 150 day wintering for the feeding period shown therein and were allowed to consume as much f d as they desired High roughage-supplement mixture ration: Percent Ground corn cobs 80 EXAMPLE 1 Soybean-molasses-vitamin-mineral 600 lb. feeder cattle- -120 day feeding period supplement 20 Control high grain-part roughage ration: Percent 100 Barley 60 lsvlolliisses 1 1 Oxytetracycline A? i ii supp ement 20 (in supplement) mg./head/day 75 a a ay Protease-cellulace enzyme combination (in supplement) grams/head/day 3 100 G 6 l Gain Ffiled t rou s eatte er rou wt. utiiza ion Gain in ree p p g p head/day) (lb. feed] Groups10 cattle per group wt. (lb./ utilization L gain) head/day) (lb. feed/ 1b. gain) gontro} antigiotic-enzyme ration. l 1. 3 13.0 on re anti iotie-enzyme ration p us Control l 8o O 20 mg. 7-ehloro5-phenyl-l-motliyl-3H- Control mtlm plus 10 1,4-bcnzodiazepin-20ll)-one 1 per head p1lG1lyl-1-m0ifllyl-3H-1,i-bBHZOdlQLZOplD- per (my 1 5 12 2 2(1H)-one l per head per day 3.15 8.6

Control rtatilon plus 1% r1)g.3I-nitir%5- (a,a,ari uoro-o-to y -l, enzo- I rliazepm-ZQID-one 1 per head per day--. 3.10 8.5 dry concentrate (20 per grams) Cob Control ration plus 10 mg. 7-nitro-5-(2- el1loropl1enyl)-3H'1,4-benzodiazepin- EXAMPLE 5 2(1H)-one 1 per head per day 3. 10 8. 6

60 lb. lambs-80-day trzal 1FedmixedinthesoybeawmineralSupplement Control high grain-part roughage ration Percent EXAMPLE 2 whole car com 8g 3. a 800 lb. beef cattle-1 00-day feeding period Molasses 4 Control corn-silage ration: Percent Soybean m l 6 Sh l d com 40 Mineral-vitamin supplement 2 Corn silage 48 Soybean-molasses-mineral supplement 12 I 100 100 Gain in Feed Groups-9 lambs per group hwt1 /(cl1b./) llgiiiZfJ-tlgI/l ea ay ee Chlortetracychne lb. ain) (as supplement) mg./head/day 75 Control ration 0. 36 4. 0 Conltrol 1ration p l slung. gelilorlotp eny-l-met 1y [-1.4- enzo iazepin-2 Gm (II-D-one 0.41 a 8 ps o cattle per group hwt.i /((l1b./) ufigizratitini c on" 01 ration plus ea ay ee UL gain) trilguoro o tolyl) 3H 1,4 ben 0' 43 3' 9 Control antibiotic ration 1. 7 16. 0

. (lH)-one 0.39 3.7

Control antlblomlc P i 2 Control ration plus hormone impla 0. 39 3. 9

cllloroi5'pheny 131'3 Control ration plus hormone implant 2 d1azepm-2(1H)-one 1 per head per day. 2.0 15. 2 plus 5 7 ch10ro 5 pheny1 1 methy1 3l-I-l,4-benzodiazepin-2(1H)-one /head/ 1 Fed mixed in the soybean-molasses-mineral supplement. day 46 6 EXAMPLE 3 Z Fed mixed in the complete ration. t d d b 50 mg. progesterone plus 5 mg. es ra ial benzoate implante su 750 lb. feeder cattle90-day feeding period glltglli30si3i between skin and curtilage of ear at the beginning of the ee lug ria. Control high grain-part roughage ration: Percent EXAMPLE 6 Grain mixture (wheat, barley, rye) 65 Molasses 75 50 lb. plgst0 market weight, 200 lbs. Protein-vitamin-mineral supplement 12.5 n- 1 fatt i ration; Percent y Ground corn 78 Soybean meal 20 100-0 Mineral-vitamin supplement 2 Stilbestrol (in supplement) mg./head/day 10 i 3 nitro-4-hydroxy-phenylarson1e acid (1n supplement) percent of ration 0.004 Gain in Feed Groups-30 cattle per group wt. (lb./ utilization head/day) (lb. ieed/ Gain in Feed 1b. gain) Groups wt. (1b.! utilization head/day) (lbb. ieed/ Control hormone ration 2. 9 8. 7 l gam) Control hormone ration plus 20 mg. 7-

ehloro-5-phenyl-1-methyl-3H-1,4-benzo- Control arsenieal ration 1 5 3 g diazepin-2(1H)one 1 per head per day 3. 2 8. 4 Control arsenieal ration plus 5 mg. 7-

chloro-dphenyl-l-methyl-3H-L4-benzod1azepiu-2(1H)-one per lb. of ration 1. (l 3. 6 1 Fed as a special dry concentrate (20 mg. per 10 grams) in the grain mixture.

5. EXAMPLE 7 Young turkey peaks-16 week study Control growing ration: Percent Corn meal 38 Soybean oil meal 37 Middlings Fish meal 5 Meat scraps 5 Fat 2 Alfalfa 2 Distillers solubles 3 Mineral vitamin supplements 3 Furazohdone (NF-180) (1n supplement) percent of ration 0.010 Amprol (in supplement) do 0.010

Gain in Feed Groups wt. (wt. utilization in lbs.) (1b. feed/ lb. gain) Control nitrofuran-coecidiostat ration.-- 14. 5 3.0 Control nitrofuran-eoccidiostat ration plus 25 mg. 7-chloro5phenyl-l-methyl- 3H-1,4-benzodiazepin-2(1H)-one per 1b. of ration 16. 0 2. 8

I claim:

1. An animal feed composition comprising nutrient material for the animal and from about 1 to about 100 mg. per pound of feed composition of a compound having the formula wherein X is selected from the group consisting of nitro and halo groups, R is selected from the group consisting of hydrogen and lower alkyl, and Y is selected from the group consisting of hydrogen, halogen, and trifluoromethyl.

2. A composition according to claim 1 wherein the compound is 7-chloro-5-phenyl-1-methy1- 3H-1,4-benzodiazepin-2(1H)-one.

3. A composition according to claim 1 wherein the compound is 7I1it1O-5- (oq,a,u-t1ifll1OI0-O-t0ly1)-3H-\1,4 benzodiazepin-2( 1H) -one.

4. A composition according'to claim 1 wherein the compound is 7-nitro-5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2(1H)-one.

5. A cattle feed comprising a feed ration for cattle and from'about 1 to about 100 mg. per pound of feed ration of a compound having the formula I ll N-C wherein X is selected from the group consisting of nitro and halo groups, R is selected from the group consisting of hydrogen and lower alkyl, and Y is selected from the group consisting of hydrogen, halogen, and trifluoromethyl, with a material whichis a nutrient for cattle.

7. An animal feed comprising nutrient material and a compound having the formula wherein X is selected from the group consisting of nitro and halo groups, R is selected from the group consisting of hydrogen and lower alkyl, and Y is selected from the group consisting of hydrogen, halogen, and trifluoromethyl, said compound being present in a proportion of from about 2 mg. to about 50 mg. per pound of said animal feed.

8. A method of producing greater weight gains in animals and increasing feed efficiency which comprises feeding an animal a composition defined in claim 1.

References Cited by the Examiner UNITED STATES PATENTS 2,893,992 7/1959 Sternbach 260--239 2,971,885 2/1961 Luther et a1. 992 3,075,968 1/1963 Krapcho 260--239 3,123,529 3/1964 Kariss et a1. 260239.3

A. LOUIS MONACELL, Primary Examiner.

D. DONOVAN, Assistant Examiner. 

1. AN ANIMAL FEED COMPOSITION COMPRISING NUTRIENT MATERIAL FOR THE ANIMAL AND FROM ABOUT 1 TO ABOUT 100 MG. PER POUND OF FEED COMPOSITION OF A COMPOUND HAVING THE FORMULA 